Abstract C114: Exploring the role of TLR4 in immune evasion and tumor progression of head and neck squamous cell carcinoma

Abstract

Abstract Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer globally and arises from the mucosal epithelium of the oral cavity, pharynx, and larynx. Bangladesh has one of the highest global incidences of head and neck cancer, estimated at 23–25 per 100,000 per year, with approximately 25,000 new cases and 16,500 deaths annually, making it a major public health concern. Inflammation plays a crucial role in tumor development, particularly through the innate immune receptor family. Among these, Toll-like receptor 4 (TLR4) is implicated in both cancer progression and anti-tumor immunity, yet its role in HNSCC carcinogenesis remains poorly understood. We aimed to investigate TLR4 expression in HNSCC and its association with immune evasion and tumor progression. In a cohort of 75 cancer patients and HNSCC cell lines (OSC-19, HSC-3, PCI-30), we observed upregulated TLR4 expression in tumor tissues and cell lines by qRT-PCR, which was corroborated at the protein level by immunofluorescence. Increased expression of inflammatory markers, including IP-10, IL-6, TNF-α, and IFN-γ, was also detected. TLR4 activation triggered inflammatory signaling in a MyD88-dependent manner, leading to pro-inflammatory cytokine upregulation and the establishment of a chronic inflammatory tumor microenvironment (TME) that favors immune suppression by recruiting regulatory T cells. Furthermore, TLR4 signaling enhanced VEGF production, thereby supporting angiogenesis. Collectively, our findings suggest that sustained TLR4-mediated inflammatory signaling in HNSCC promotes tumor growth, facilitates immune escape, and reshapes the TME in favor of tumor progression. These data underscore the pivotal role of TLR4 in the HNSCC immune landscape and highlight TLR4 signaling as a potential therapeutic target. Citation Format: Sunanda Baidya, Utpal Barua, Muntasim Rahman, Md. Rakibul Islam, Arpa Dey, Arafat Hossain. Exploring the role of TLR4 in immune evasion and tumor progression of head and neck squamous cell carcinoma [abstract]. In: Proceedings of the 19th AACR Conference on the Science of Cancer Health Disparities; 2026 Oct 18-21; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2026;35(10 Suppl):Abstract nr C114.